Stroke is the second leading cause of death in the world with an even greater burden of major disability. It occurs at all ages with the greatest incidence in the elderly. The number of stroke is expected to rise in the US and the world as the population ages. Its estimated direct and indirect cost in the U.S. for 2013 is $109.6 billion. In 2013, the National Institute of Neurological Disorders and Stroke (NINDS) formed a network of stroke clinical trials centers to prioritize and efficiently design and conduct exploratory (Phase II) and confirmatory (Phase III) clinical stroke trials as well as to provide a mechanism for training of the next generation of clinical stroke researchers. The NIH StrokeNet is a multidisciplinary stroke research infrastructure that includes a National Clinical Coordinating Center, a National Data Management Center (NDMC), 25 Regional Coordinating Centers and their associated regional hospitals, and the NINDS. Its mission is to develop and test new therapies for stroke treatment, recovery, and prevention that can decrease the global burden of stroke. The NCC's roles are to establish and foster a collaborative relationship with all parties involved in the Network, to provide scientific and operational leadership in the development and execution of the stroke trials, and to oversee the educational development of StrokeNet fellows within StrokeNet. From a scientific standpoint, we have established three stroke working groups (acute, prevention and recovery/rehabilitation) that are led by senior clinical investigator leaders from the NCC with appropriate expertise. These working groups help PIs of clinical trial proposals with the scientific design and feasibility of a given trial. An imaging core, and four advisory committees (minority recruitment and retention, endovascular, pediatrics and ethics), centered within the NCC, also provide input to clinical trial development and execution. Operationally, the NCC houses the Central IRB (CIRB) for ongoing StrokeNet Trials that involves reliance agreements between the University of Cincinnati and over 300 local institutions, one of the largest IRB reliance networks in the U.S. The NCC is responsible for master trial agreements for all RCCs and the 381 participating hospital sites, all financial payments to participating sites regarding trial tasks, and the overall clinical study management of ongoing trials working with the respective PIs. Finally, the NCC houses the educational and mentoring core for the StrokeNet that provide education and training regarding stroke and stroke research to a broad base of diverse individuals within NIH StrokeNet (at least one fellow per RCC per year).